Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS). Although the etiology of MS is not known, there is considerable indirect evidence to suggest the role of infectious agents in the development of the disease. While a viral agent is still strongly considered, efforts to defect a virus in patients with MS have failed. We present preliminary data which argue that Chlamydiae Pneumoniae may be a candidate pathogen in MS. This inference is based on: a) the presence of PCR products to major outer membrane protein (MOMP) gene of C. pneumoniae in the cerebrospinal fluid (CSF) of patients with secondary progressive MS but not in other neurologic disease controls (OND); b) the presence of antibody to C. pneumonia antigens in the CSF of MS patients; and c) the presence of chlamydial antigens in brain autopsy specimens of patients who have died of MS. C. pneumoniae belongs to a genus of intracellular pathogens that are infectious to humans and other vertebrates. C. pneumoniae are implicated in many chronic diseases, including those presumed to be autoimmune. Chlamydiae cause chronic persistent inflammation in humans and other vertebrate animals and tissue injury in all cases appears to be immune mediated. Immune activation by C. pneumoniae includes induction of T cell response to heat shock proteins and production of pro-inflammatory cytokines. Our proposal sets out to meet the necessary criteria required to attribute a causal association between C. pneumoniae and MS. These would include the ability to detect the organism either directly by culture or by demonstrating the presence of C. pneumoniae DNA and mRNA and evidence of intracytoplasmic or organisms as proven by electron microscopy in the CNS tissue of patients with MS. Also, the presence of an immune response to C. pneumoniae that is contained within the CNS compartment will constitute strong circumstantial evidence of microbial infection.